Contacts:

Sharon Tetlow diaDexus, Inc. (650) 246-6400

Rick Koenig GlaxoSmithKline (610) 270-5546

NOVEL CARDIOVASCULAR MARKER PREDICTS RISK OF STROKE

New data show individuals with highest Lp-PLA2 levels are at 2-fold higher risk

South San Francisco, CA - May 8, 2004 - Elevated levels of an enzyme implicated in atherosclerosis are significantly associated with an increased risk of stroke, researchers reported here today at the 5th Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology. The risk of stroke for individuals with the higher levels of the enzyme, called Lp-PLA2 (lipoprotein-associated phospholipase A2), was double that for individuals with the lower levels of the enzyme.

This finding from the Atherosclerosis Risk in Communities (ARIC) Study builds on data from previous studies showing that Lp-PLA2 is a strong and independent marker for coronary heart disease.

"These new data further support the predictive value of Lp-PLA2, demonstrating its link to strokes as well as to heart attacks," said Christie M. Ballantyne, M.D., director of the Center for Cardiovascular Disease Prevention at Baylor College of Medicine and the Methodist DeBakey Heart Center, Houston, and lead investigator of this study. "Our results also support further investigation of Lp-PLA2 as a potential target for therapy."

GlaxoSmithKline (GSK) is actively investigating Lp-PLA2 inhibitors and the role they may play in further reducing the risk of cardiovascular disease. Cardiovascular disease is one of the leading causes of death and disability around the world. Atherosclerosis, which is now recognized to be an inflammatory disease, is the underlying process in the great majority of heart attacks and strokes, and despite the use of cholesterol-lowering drugs (for example, statins) and other agents, millions of patients remain at risk. The discovery of new risk markers such as Lp-PLA2 is likely to be critical in further reducing the global burden of cardiovascular disease.

The data presented today are the latest results from the ARIC study, a landmark epidemiological investigation of atherosclerosis and its causes in more than 15,000 apparently healthy men and women in the US aged from 45 to 64 years.¹ This prospective, case-cohort study of the ARIC population examined the relationship between Lp-PLA2, C-reactive protein (CRP) and traditional risk factors and the incidence of stroke over approximately six years. The results showed that mean levels of both Lp-PLA2 and CRP were higher in the 223 men and women who suffered strokes than in a cohort random sample of 766 who did not suffer strokes.

When patients were ranked according to their Lp-PLA2 levels and separated into three groups of equal size, the risk of stroke in the group with the highest levels of Lp-PLA2 (>422 ug/L) was more than double that in the group with the lowest levels of Lp-PLA2 (<310 ug/L). The findings also indicate that Lp-PLA2 is a strong and independent risk marker for stroke irrespective of traditional risk factors (for example, age, sex, race, smoking, and blood pressure), low-density lipoprotein (LDL)-cholesterol (sometimes called "bad cholesterol"), high-density lipoprotein (HDL)-cholesterol (sometimes called "good cholesterol"), triglycerides, or body-mass index.

Moreover, the risk was independent and additive to that associated with CRP, a marker of systemic inflammation. After taking into consideration traditional risk factors, individuals with the highest levels of both Lp-PLA2 and CRP were shown to have a greater than 8-fold (95% confidence interval 3-25) higher risk of stroke compared with those with the lowest levels of both Lp-PLA2 and CRP. In this study, as in a previous analysis of the ARIC study,² LDL-C levels did not predict risk of stroke. The role of LDL-C in ischemic stroke from other studies to date is inconclusive.

This investigation of the ARIC population was funded by the National Heart, Blood and Lung Institute and GSK.

Atherosclerosis, which develops as fatty plaques within arterial walls, underlies both stroke and heart attack. The role of inflammation in atherosclerosis has become well established over the past decade, and a growing body of evidence now indicates that Lp-PLA2 promotes inflammation in atherosclerotic plaque by acting upon oxidized LDL so as to produce pro-inflammatory substances.

Inhibiting Lp-PLA2 thus offers the prospect of reducing strokes and heart attacks by decreasing vascular inflammation. GSK has several Lp-PLA2 inhibitors in clinical studies.

Lp-PLA2 levels in the ARIC population were measured using the PLAC® test, developed and commercialized by diaDexus, a privately held biotechnology company. This blood test was cleared by the U.S. Food and Drug Administration to aid in the prediction of an individual's risk for a coronary-heart-disease event, in conjunction with clinical evaluation and patient risk assessment. The PLAC® test was based on discoveries and developments by GSK and is currently available through clinical diagnostics laboratories throughout the USA. For more information on the PLAC® test, visit www.plactest.com.

Data from studies of the ARIC population have been published in more than 380 articles in peer-reviewed journals. Approximately 400 abstracts of ARIC data have been presented at national and international scientific conferences and meetings.

About GlaxoSmithKline
GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, visit www.gsk.com.

About diaDexus
diaDexus, Inc., a privately held biotechnology company, based in South San Francisco, California, is focused on the discovery, development and commercialization of novel, patent-protected diagnostic and therapeutic products with high clinical value. More information about the company and the PLAC® test may be found at www.diaDexus.com and www.plactest.com.

References

1. Lipoprotein-Associated Phospholipase A2 (Lp-PLA2), High-Sensitivity C-Reactive Protein (hs-CRP), and Risk for Incident Stroke in Middle-Aged Men and Women in the Atherosclerosis Risk in Communities (ARIC) Study, CM Ballantyne, et al. Presented at the 5th Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology, San Francisco, CA, May 8, 2004.

2. Plasma Lipid Profile and Incident Ischemic Stroke: The Atherosclerosis Risk in Communities (ARIC) Study, E Shahar, LE Chambless, WD Rosamond, et al. Stroke. 2003;34:623-631.